A placebo-controlled, double-blind, randomized, multicenter study to assess the effects of dronedarone 400 mg twice daily for 12 weeks on atrial fibrillation burden in subjects with permanent pacemakers

PURPOSE: Dronedarone is a benzofuran derivative with a pharmacological profile similar to amiodarone but has a more rapid onset of action and a much shorter half-life (13-19 h). Our goal was to evaluate the efficacy of dronedarone in atrial fibrillation (AF) patients using dual-chamber pacemakers capable of quantifying atrial fibrillation burden. METHODS: Pacemakers were adjusted to optimize AF detection. Patients with AF burden >1% were randomized to dronedarone 400 mg twice daily (BID) or placebo. Pacemakers were interrogated after 4 and 12 weeks of treatment. The primary endpoint was the change in AF burden from baseline over the 12-week treatment period. Patients with permanent AF, severe/recently decompensated heart failure, and current use of antiarrhythmic drugs were excluded. AF burden was assessed by a core laboratory blinded to treatment assignment. RESULTS: From 285 patients screened, 112 were randomized (mean age 76 years, 60% male, 84% hypertensive, 65% with sick sinus syndrome, 26% with diabetes mellitus type II, 15% with heart failure). Baseline mean (SEM) AF burden was 8.77% (0.16) for placebo and 10.14% (0.17) for dronedarone. Over the 12-week study period, AF burden compared to baseline decreased by 54.4% (0.22) (P = 0.0009) with dronedarone and trended higher by 12.8% (0.16) (P = 0.450) with placebo. The absolute change in burden was decreased by 5.5% in the dronedarone group and increased by 1.1% in the placebo group. Heart rate during AF was reduced to approximately 4 beats/min with dronedarone (P = 0.285). Adverse events were higher with dronedarone compared to placebo (65 vs 56%). CONCLUSIONS: Dronedarone reduced pacemaker-assessed the relative AF burden compared to baseline and placebo by over 50% during the 12-week observation period.